PUBLICATION

Single-cell RNA sequencing unravels the transcriptional network underlying zebrafish retina regeneration

Authors
Celotto, L., Rost, F., Machate, A., Bläsche, J., Dahl, A., Weber, A., Hans, S., Brand, M.
ID
ZDB-PUB-231122-15
Date
2023
Source
eLIFE   12: (Journal)
Registered Authors
Brand, Michael, Hans, Stefan, Machate, Anja
Keywords
developmental biology, light lesion, progenitors, regeneration, retina, scRNAseq, zebrafish
Datasets
GEO:GSE226373
MeSH Terms
  • Animals
  • Cell Proliferation
  • Gene Regulatory Networks*
  • Humans
  • Nerve Regeneration/genetics
  • Neuroglia/metabolism
  • Retina/physiology
  • Sequence Analysis, RNA
  • Zebrafish*/metabolism
PubMed
37988404 Full text @ Elife
Abstract
In the lesioned zebrafish retina, Müller glia produce multipotent retinal progenitors that generate all retinal neurons, replacing lost cell types. To study the molecular mechanisms linking Müller glia reactivity to progenitor production and neuronal differentiation, we used single-cell RNA sequencing of Müller glia, progenitors and regenerated progeny from uninjured and light-lesioned retinae. We discover an injury-induced Müller glia differentiation trajectory that leads into a cell population with a hybrid identity expressing marker genes of Müller glia and progenitors. A glial self-renewal and a neurogenic trajectory depart from the hybrid cell population. We further observe that neurogenic progenitors progressively differentiate to generate retinal ganglion cells first and bipolar cells last, similar to the events observed during retinal development. Our work provides a comprehensive description of Müller glia and progenitor transcriptional changes and fate decisions in the regenerating retina, which are key to tailor cell differentiation and replacement therapies for retinal dystrophies in humans.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping